This invention pertains to a method for enhancing antioxidant levels in human beings without administration of exogenous antioxidants through diet or supplements.
Oxidative stress is thought to be involved in the aging process in aerobic organisms and to play a role in the pathogenesis of several disease states, including Alzheimer""s disease, myocardial infarction, atherosclerosis, Parkinson disease, autoimmune diseases, radiation injury, emphysema, sunburn, glomerular disorders, schizophrenia, sickle cell disease, leukemia, osteoporosis, infertility, cancer, retinopathy, and noise-related hearing impairment. Oxidative stress is the result of free radicals, such as the hydroxyl radical, reacting with biological macromolecules, such as lipids, proteins, nucleic acids and carbohydrates. The initial reaction generates a second radical, which in turn can react with a second macromolecule to continue the chain reaction. In the process of reacting, a free radical can modify protein or DNA structures, disrupt individual nucleotide bases, and thereby cause effects such as single-strand breaks and cross-linking in nucleic acids. Free radical-induced oxidative stress has been associated with a number of major cardiovascular disease risk factors. See xe2x80x9cReactive Oxygen Species (ROS)xe2x80x9d (first printed in R and D Systems"" 1997 Catalog), available at http://www.rndsystems.com/asp/g_sitebuilder.asp?bodyId=222.
A current theory holds that free radical-induced oxidative stress is a major factor in the long-term tissue degradation associated with aging. This free radical theory proposes that aging is the cumulative result of oxidative damage to the cells and tissues of the body that arises primarily as a result of aerobic metabolism. Several lines of evidence have been used to support this hypothesis including the claims that: (1) Variation in species life span is correlated with metabolic rate and protective antioxidant activity; (2) enhanced expression of antioxidative enzymes in experimental animals can produce a significant increase in longevity; (3) cellular levels of free radical damage increases with age; and (4) reduced calorie intake leads to a decline in the production of free radical and an increase in life span. The free radical theory may also be used to explain many of the structural features that develop with aging including the lipid peroxidation of membranes, formation of age pigments, cross-linkage of proteins, DNA damage and decline of mitochondrial function. Wickens, A. P., xe2x80x9cAgeing and the free radical theory,xe2x80x9d Respir. Physiol., Vol. 128(3), pp. 379-91 (2001).
Free radicals only occur in trace quantities in biological tissues and are extremely reactive. Because of the difficulty of directly measuring free radicals in vivo, measurements can be made using biomarkers, for example, an assay of antioxidant vitamins and free radical scavengers. Therefore, oxidative stress has been mainly observed through such indirect biomarkers of free radical-induced damage. In aerobic organisms, oxidative damages to tissues and organs is prevented by a network of defenses which include antioxidant and repairing enzymes, as well as small molecules with scavenging ability, such as antioxidant vitamins. For these reasons, the assay of antioxidant vitamins and of small molecular free radical scavengers in biological milieus may be used, if appropriately performed, to quantify the defense status against oxidative damage and to provide an indirect estimate of free radical production in aging humans. Polidori, M. C., et al., xe2x80x9cPeripheral non-enzymatic antioxidant changes with human aging: a selective status report,xe2x80x9d Biogerontology, Vol. 2(2), pp. 99-104 (2001).
Malondialdehyde (MDA) levels both in blood and urine have been one of the most widely used free radical markers. Measurement of MDA excretion in the urine became available in 1964. MDA is the end product of lipid peroxidation, and this urinary calorimetric assay represents by far the simplest approach to measurement of free radical activity. Furthermore, this colorimetric assay has been highly statistically significantly correlated with the fluorometric approach.
Mammalian cells possess elaborate defense mechanisms to detoxify radicals. Radical-scavenging antioxidants (e.g., vitamin E) interrupt the chain by capturing the radical; the vitamin E radical is relatively stable, and it can be enzymatically converted to its non-radical form. Excessive amounts of cellular oxidants, which animal cells constantly produce, can induce oxidative damage. Cellular antioxidants provide a defense against the damaging effects of the cellular oxidants. However, in moderate concentrations, cellular oxidants are necessary for a number of protective reactions which eliminate cancerous and other life-threatening cells, such as anti-microbial phagocytosis and apoptosis. Excess antioxidants could inhibit the protective anti-cancer function that the apoptosis process provides. Abundant antioxidants might suppress these protective functions, particularly in people with a low innate baseline level of cellular oxidants. Salganik, R. I., xe2x80x9cThe benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population,xe2x80x9d J. Am. Coll. Nutr., Vol. 20(5 Suppl.), pp. 464S-472S (2001).
Conventional antioxidant supplements comprise, for example, vitamin C, vitamin E, beta-carotene, or other forms such as red ginseng or DHEAs, for example. Given that antioxidant supplements can actually be harmful in high doses to patients who have low levels of baseline cellular oxidants, safe antioxidant supplement use requires an accurate dosage level corresponding to each patient""s needs. Each patient""s baseline needs would have to be determined periodically because it is also clear that the optimal dosage of antioxidant supplements probably varies over time with each patient. Meagher, E., et al., xe2x80x9cAntioxidant therapy and atherosclerosis: animal and human studies,xe2x80x9d Trends Cardiovasc. Med., Vol. 11 (3-4), pp. 162-5 (2001).
In healthy individuals, a delicate balance exists between the production of free radicals and the production of antioxidants. Free radicals are produced in the body as byproducts of normal metabolism and as a result of exposure to radiation and some environmental pollutants. They are normally neutralized by the body""s production of antioxidant enzymes (super oxide dismutase, catalase, and glutathione peroxidase) and the nutrient-derived antioxidant small molecules (Vitamin E, Vitamin C, carotene, flavonoids, glutathione, uric acid, and taurine). In some pathological conditions, the natural balance can be upset by oxidative stress in the presence of certain diseases, such as diabetes. The oxidative stress can cause a reduction in the body""s normal production of antioxidants. To prevent deterioration of antioxidant levels, it is conventionally recommended to consume adequate amounts of antioxidant-rich foods, e.g., fruits and vegetables, and also to take supplements as necessary. Sardesai, V. M., xe2x80x9cRole of antioxidants in health maintenance,xe2x80x9d Nutr. of Clin. Pract., Vol. 10(1), pp. 19-25 (1995).
Despite the extensive research in the use of antioxidants, there is not a clear-cut consensus that these antioxidants are totally successful in reducing free radicals. Sacheck, J. M., et al., xe2x80x9cRole of Vitamin E and Oxidative Stress in Exercise,xe2x80x9d Nutrition, Vol. 27(10), pp. 809-14 (2001), Meagher, E., et al., xe2x80x9cAntioxidant Therapy and Atherosclerosis: Animal and Human Studies,xe2x80x9d Trends Cardiovasc. Med., Vol. 11(3-4), pp. 162-5 (2001). Although cancer tissue has significant decreases in glutathione, vitamin C, and vitamin E, there is no evidence that taking the supplements actually prevents cancer. Skrzydlewska, E., et al., xe2x80x9cAntioxidant Status and Lipid Peroxidation in Colorectal Cancer,xe2x80x9d Toxicol. Environ. Health A., Vol. 64(3), pp. 213-22 (2001). On the other hand, there is considerable evidence that the antioxidants found in natural sources, such as vegetables and fruits, do have a beneficial effect. Trichopoulou, A., et al., xe2x80x9cGuidelines for the Intake of Vegetables and Fruit: The Mediterranean Approach,xe2x80x9d Int. J. Vitam. Nutr. Res., Vol. 71(3), pp. 149-53 (2001). Despite the lack of great clinical significance in the use of antioxidants, there is a great argument for the use of micronutrient antioxidants as a standard in many diseases, including cancer and Type 2 diabetes. It is also of some interest that the antioxidants themselves apparently do not ordinarily cross the blood brain barrier, a significant problem in reducing the known negative effects of free radicals in many degenerative central nervous system diseases, such as Alzheimer""s. Blass, J. P., xe2x80x9cBrain Metabolism and Brain Disease: Is Metabolic Deficiency the Proximate Cause of Alzheimer Dementia?xe2x80x9d J. Neurosci. Res., Vol. 66(5), pp. 851-56 (2001). Finally, an effective antioxidant supplement regimen can be expensive to maintain.
Other than antioxidants, there is only one known non-antioxidant technique for reducing free radicals. That is, 6 degrees head down bed rest; however, that can require as much as 17 days of simulated weightlessness. Furthermore, bed rest and the corresponding inactivity have also been linked to increased free radical levels. Peng, Y., et al., xe2x80x9cEffects of Hyposi and Qigong on Urine Malondialdehyde, Superoxide Dismutase and Circulating Endothelial Cell in Humans During Simulated Weightlessness,xe2x80x9d Space Med. Eng. (Beijing), Vol. 11 (2), pp. 136-8 (1998); Pawlak, W., et al., xe2x80x9cEffect of Long Term Bed Rest in Men on Enzymatic Antioxidative Defence and Lipid Peroxidation in Erythrocytes,xe2x80x9d J. Gravit. Physiol., Vol. 5(1), pp. 163-4 (1998).
It has been disclosed that treating a patient with electrical stimulation at acupuncture points known as the xe2x80x9cRing of Air,xe2x80x9d can endogenously increase serum neurotensin levels in living human beings. See U.S. Pat. No. 6,233,489. It has also been disclosed that treating a patient with electrical stimulation at acupuncture points known as the xe2x80x9cRing of Firexe2x80x9d can increase serum dehydroepiandrosterone (DHEA) levels. See U.S. Pat. No. 5,109,847. Until now, however, there has been no known method of reducing free radical levels in a living human being in a manner similar to the xe2x80x9cRing of Airxe2x80x9d or xe2x80x9cRing of Firexe2x80x9d electrical stimulation.
The present invention provides a method for enhancing or restoring antioxidant levels in a living human being. Because antioxidants are naturally occurring in the human body, in accordance with the present invention endogenous production of antioxidants may be stimulated without requiring the use of exogenous dietary supplements or pharmaceutical preparations containing antioxidants or antioxidant analogs.
Antioxidants levels in human beings may be raised without the use of dietary supplements or pharmaceuticals by applying electrical stimulation to specific epidermal points of the individual""s body for a period of time, preferably daily. The electrical stimulation is preferably applied to specific locations on the individual""s body which correspond to 13 well-known acupuncture points known as the xe2x80x9cRing of Crystal.xe2x80x9d The electrical stimulation can be applied to these acupuncture points over a number of weeks to achieve a significant increase in antioxidant levels and a corresponding decrease in free radical activity within the patient. Preferably, electrical stimulation is applied for a minimum period of 2 to 4 weeks.
Electrical stimulation of the Ring of Crystal acupuncture points on the human body, in accordance with the present invention, has been shown to be highly efficacious among 80 percent of subjects tested in reducing free radicals, and it does not appear to risk potentially excessive antioxidants levels that may be produced by increased dosages of exogenous antioxidant supplements.
Further objects, features and advantages of the invention will be apparent from the following detailed description taken in conjunction with the accompanying drawings.